NM_000152.5(GAA):c.1019A>G (p.Tyr340Cys) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 30, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002469100.1

Allele description [Variation Report for NM_000152.5(GAA):c.1019A>G (p.Tyr340Cys)]

NM_000152.5(GAA):c.1019A>G (p.Tyr340Cys)

Gene:

GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.1019A>G (p.Tyr340Cys)

Other names:

NM_000152.5(GAA):c.1019A>G; p.Tyr340Cys

HGVS:

NC_000017.11:g.80108353A>G
NG_009822.1:g.11798A>G
NM_000152.5:c.1019A>GMANE SELECT
NM_001079803.3:c.1019A>G
NM_001079804.3:c.1019A>G
NP_000143.2:p.Tyr340Cys
NP_001073271.1:p.Tyr340Cys
NP_001073272.1:p.Tyr340Cys
LRG_673t1:c.1019A>G
LRG_673:g.11798A>G
NC_000017.10:g.78082152A>G
NM_000152.3:c.1019A>G
NM_000152.4:c.1019A>G

Protein change:

Y340C

Links:

dbSNP: rs144857480

NCBI 1000 Genomes Browser:

rs144857480

Molecular consequence:

NM_000152.5:c.1019A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001079803.3:c.1019A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001079804.3:c.1019A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002765937	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Nov 30, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 33073007, 32802993 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002765937

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Nov 30, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The First Year Experience of Newborn Screening for Pompe Disease in California.

Tang H, Feuchtbaum L, Sciortino S, Matteson J, Mathur D, Bishop T, Olney RS.

Int J Neonatal Screen. 2020 Mar;6(1):9. doi: 10.3390/ijns6010009.

PubMed [citation]

PMID:: 33073007
PMCID:: PMC7422988

A Comparative Effectiveness Study of Newborn Screening Methods for Four Lysosomal Storage Disorders.

Sanders KA, Gavrilov DK, Oglesbee D, Raymond KM, Tortorelli S, Hopwood JJ, Lorey F, Majumdar R, Kroll CA, McDonald AM, Lacey JM, Turgeon CT, Tucker JN, Tang H, Currier R, Isaya G, Rinaldo P, Matern D.

Int J Neonatal Screen. 2020 Jun;6(2). doi:pii: 44. 10.3390/ijns6020044. Epub 2020 May 30.

PubMed [citation]

PMID:: 32802993
PMCID:: PMC7423013

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002765937.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: GAA c.1019A>G (p.Tyr340Cys) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6e-05 in 251104 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (6e-05 vs 0.0042), allowing no conclusion about variant significance. c.1019A>G has been reported in the literature in patients with unknown phenotypes (Sanders_2020, Tang_2020). These reports do not provide unequivocal conclusions about association of the variant with Glycogen Storage Disease, Type 2 (Pompe Disease). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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